SummaryBackgroundRemote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months.MethodsWe did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed.FindingsBetween Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91–1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed.InterpretationRemote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI.FundingBritish Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden.

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The superiority of dabigatran has been well proven in the standard dosing regimen in prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) and extended venous thromboembolism (VTE) treatment. Dabigatran, an anticoagulant with a good safety profile, reduces intracranial bleeding in patients with atrial fibrillation and decreases major and clinically relevant non-major bleeding in acute VTE treatment. However, several important clinical issues are not fully covered by currently available directions with regard to dabigatran administration. The prominent one is reflected in the fact that dynamic impairment in renal function due to dehydratation may lead to haemorragic complications on the one hand, while on the other hand glomerular hyperfiltration may be a possible cause of dabigatran subdosing, hence reducing the drug's efficacy. Furthermore, limitations of the Cockcroft-Gault formula, considered a standard equation for assessing the renal function, may imply that other calculations are likely to obtain more accurate estimates of the kidney function in specific patient populations. Method and Conclusions: Although not routinely recommended, a possibility of monitoring dabigatran in special clinical settings adds to optimization of its dosage regimens, timely perioperative care and administration of urgently demanded thrombolytic therapy, therefore significantly improving this drug's safety profile. Despite the fact that dabigatran has fewer reported interactions with drugs, food constituents, and dietary supplements, certain interactions still remain, requiring considerable caution, notably in elderly, high bleeding risk patients, patients with decreased renal function and those on complex drug regimens. Additionally, upon approval of idarucizumab, an antidote to dabigatran solution, hitherto being a major safety concern, has been finally reached, which plays a vital role in life-threatening bleeding and emergency interventions and surgery.

The present study demonstrated that bleeding events defined according to the BARC classification hierarchically correlate with 1-year mortality after admission for primary PCI. The strongest predictor of 1-year mortality is the BARC type 3b bleeding.

Patients of advanced age, female gender, with baseline anemia and elevated WBC count and those with Killip class II-IV at presentation are at particularly high risk of bleeding after primary PCI. Bleeding is associated with adverse outcome and may be an important marker of patient frailty, but it is not a true independent predictor of mortality/MACE.

AimsIn heart failure, various biomarkers are established for diagnosis and risk stratification; however, little is known about the relevance of serial measurements during an episode worsening heart failure (WHF). This study sought to investigate the trajectory of natriuretic peptides and multiple novel biomarkers during hospitalization for WHF and to determine the best time point to predict outcome.Methods and resultsMOLITOR (Impact of Therapy Optimisation on the Level of Biomarkers in Patients with Acute and Decompensated Chronic Heart Failure) was an eight‐centre prospective study of 164 patients hospitalized with a primary diagnosis of WHF. C‐terminal fragment of pre‐pro‐vasopressin (copeptin), N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), mid‐regional pro‐atrial natriuretic peptide (MR‐proANP), mid‐regional pro‐adrenomedullin (MR‐proADM), and C‐terminal pro‐endothelin‐1 (CT‐proET1) were measured on admission, after 24, 48, and 72 h, and every 72 h thereafter, at discharge and follow‐up visits. Their performance to predict all‐cause mortality and rehospitalization at 90 days was compared. All biomarkers decreased during recompensation (P < 0.05) except MR‐proADM. Copeptin at admission was the best predictor of 90 day mortality or rehospitalization (χ 2 = 16.63, C‐index = 0.724, P < 0.001), followed by NT‐proBNP (χ 2 = 10.53, C‐index = 0.646, P = 0.001), MR‐proADM (χ 2 = 9.29, C‐index = 0.686, P = 0.002), MR‐proANP (χ 2 = 8.75, C‐index = 0.631, P = 0.003), and CT‐proET1 (χ 2 = 6.60, C‐index = 0.64, P = 0.010). Re‐measurement of copeptin at 72 h and of NT‐proBNP at 48 h increased prognostic value (χ 2 = 23.48, C‐index = 0.718, P = 0.00001; χ 2 = 14.23, C‐index = 0.650, P = 0.00081, respectively).ConclusionsThis largest sample of serial measurements of multiple biomarkers in WHF found copeptin at admission with re‐measurement at 72 h to be the best predictor of 90 day mortality and rehospitalization.

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